The submitted application for a K01 Mentored Scientist Career Development Award will afford Dr. Nicole Nugent formal and tailored training essential for her programmatic line of research in genetic predictors of psychiatric functioning (e.g., depression, anxiety, substance abuse), health behaviors (e.g., medication adherence, sex risk), and health outcomes (e.g., CD4/CD8 lymphocytes, HIV-1 plasma RNA levels, cytokines, and natural killer cells) in youth living with HIV (YLH). Given that YLH evidence levels of non- adherence to antiretroviral regimens expected to result in drug resistance and virologic failure, thereby increasing likelihood of transmission of drug-resistant strains to others, the public and patient health relevance elucidating factors that may influence health behaviors is substantial. Select genetic variants may influence patient health outcomes via their effects on synergistic neurobiological and psychobehavioral processes. Genetic samples and longitudinal data collected through the Reaching for Excellence in Adolescent Care and Health (REACH) Project provide a unique, cost-effective opportunity to examine these aims. Additionally, the proposed research is ideally suited to Dr. Nugent's career and training goals to: (1) obtain sufficient training in molecular genetics to permit informed multidisciplinary research collaborations with molecular genetics and other scientists, (2) gain expertise in advanced statistical modeling of genetic variants influencing human behavior and psychiatric conditions, (3) obtain familiarity with genetic influences on HIV transmission and post-infection disease progression, (4) further sensitivity to ethical considerations in genetic research and research with stigmatized populations, and to establish herself as a contributor within the psychiatric genetic and adolescent HIV scientific fields. These training goals will be achieved through a combination of formal coursework and workshops, applied training experiences using REACH and mentor data, and ongoing close mentorship. This K01 award will permit training and research findings to support future planned ROIs and programmatic line of innovative research with YLH. PUBLIC HEALTH RELEVANCE: Although antiretroviral therapy has afforded marked health gains in YLH, these benefits are limited by patient adherence. Non-adherence results in emergence of drug-resistant strains of HIV. Identification of factors that may contribute to health outcomes in YLH via their effects on psychobehavioral and/or neurobiological processes will permit the development of informed behavioral and pharmacologic interventions for YLH.